This proposal is based on the observation that the apparent diffusivity of several small solutes is aberrantly rapid in a matrix of isolated hyaluronic acid as well as in synovial fluid. The ability to enhance the movement of a solute such as glucose is inversely dependent on the intrinsic viscosity of the hyaluronate. Enhanced diffusivity is observed in dense (2.5%) matrices. Dilute matrices (1%) will support enhanced diffusivity if a low molecular weight cationic serum species is incorporated into the solvent. Analysis of the permeability and viscoelastic properties of the hyaluronate matrix as well as 13C-nuclear magnetic resonance (NMR) analysis suggests that the small solutes interact with the hyaluronate matrix in a fashion that facilitates their translational diffusivity. The objective of this proposal is to extend these observations: The small cationic serum species that endows the hyaluronate matrix with the ability to enhance solute diffusivity will be further defined. Features of matrix structure prerequisite to enhanced diffusivity will be detailed. The structure of isolated hyaluronate matrices at varying pH, temperature, ionic strength, and degree of polymerization will be defined in terms of viscoelastic properties, permeability, and natural abundance 13C-NMR spectra. In parallel, the behavior of small solutes in these defined matrices in terms of diffusivity will be examined. Finally we shall return to pathological synovial fluids to establish the relevance of the variables to articular diseases. Such an approach should provide insights into the mechanisms of interaction of small solutes with hyaluronate that facilitate their movement.